A physiologic measure of chronic pain is the fervent hope of many researchers, but achieving such a “biomarker” requires two intertwined advances: a measurement technique that is sensitive to ongoing pain, and a readout that meaningfully relates to patients’ experiences. A new study makes headway on both fronts. Researchers have applied arterial spin labeling, a less frequently used type of functional magnetic resonance imaging (fMRI), to study brain activity in patients with chronic low back pain. They found that, as subjects’ pain worsened, brain activation occurred in “pain matrix” regions as well as in areas that contribute to attention. The study, from Ajay Wasan and colleagues at Brigham and Women’s Hospital and Massachusetts General Hospital, both in Boston, appears in the August issue of Anesthesiology and was published online June 30.
A variety of imaging strategies have been used to investigate neural activity in pain. However, as Irene Tracey and Emily Johns, University of Oxford, U.K., wrote last year, “There has always been an ‘elephant in the room’” (Tracey and Johns, 2010). The studies, they said, “do not measure activity related to ongoing, background pain.” In particular, studies that use blood oxygen level dependent (BOLD) contrast require that a subject’s pain be changing rapidly during imaging, such as in response to applied stimuli.
Arterial spin labeling (ASL) perfusion contrast scanning, an fMRI variant that tracks the signal of magnetized endogenous water in blood, is emerging as a possible solution. Unlike BOLD, the technique provides an absolute measure of blood flow in the brain. It does not require a quickly changing stimulus, which recommends it as a metric of slowly evolving changes, such as those that occur in ongoing pain.
Researchers are just beginning to apply ASL to chronic pain. One recent study looked at brain activity in a model of tonic muscular pain (Owen et al., 2009), and another analyzed changes during migraine and treatment (Kato et al., 2010).
In the new study, Wasan and coworkers modeled the varying pain of patients with chronic low back pain. To start, 16 patients rated their existing pain, and ASL brain scanning was performed. The patients then underwent a series of standardized maneuvers to exacerbate their pain, such as straight leg raising. During the maneuvers, patients’ reported pain increased acutely; then, when the movement was stopped, the pain dropped back to a lower (“baseline”) level. Over the course of a series of leg lifts, baseline pain crept up 34 percent. At the end of the session, a second ASL scan was performed.
A variety of brain regions showed significant increases in blood flow after the painful maneuvers. Wasan sees two key themes in the findings: First, many areas known to be activated by acute pain were also activated in this study during worsening of chronic pain. Second, regions involved in attention such as the superior parietal lobules, which, Wasan says, have been associated more with chronic pain, were strongly activated by the manipulations. By comparison, pain-free control subjects who were put through the protocol showed no statistically significant changes in brain blood flow.
The researchers did not observe a linear relationship between degree of blood flow and increase in pain. That is, the scans did not provide a quantitative metric of patients’ pain reports. Even so, Wasan believes they do reflect meaningful shifts in patients’ experiences.
In support of that idea, when patients were exposed to painful heat, brain blood flow did not increase, even though baseline pain did ramp up by 19 percent. That increase was somewhat less than the 34 percent jump in pain caused by leg lifting, and suggests what Wasan calls a threshold effect: Only when pain increased by more than 30 percent did changes show up in the scans. That threshold aligns with previous findings that pain intensity changes of greater than 30 percent are clinically relevant. “What we’re ultimately trying to do is tie brain activity to experiences of patients. Patients don’t necessarily think about their pain as being 10 percent worse. They think…is this a lot worse today?” Wasan told PRF.
Following up on this study, Wasan says the team is now applying ASL to studies of other chronic pain conditions. They are also looking at patients undergoing treatment to see how brain activity changes as pain is alleviated.
While this and other studies are suggesting that ASL could be a useful marker of pain fluctuations, Wasan notes that nothing is known yet about whether the technique could be used as a biomarker to identify the underlying neurobiology of pain in individual patients, and thus treat them more effectively.